1. What is so memorable about CREBBP? (RSTS; RTS, CBP CBP/MOZ FUSION GENE, CREB-binding protein)

2. Where is it found?

3. What exactly does “BP” mean Binding protien What is a coactivator and what is its role? Does it perform one function (interaction) or does it perform many? pg224 of book http://www.ebi.ac.uk/intact/search/do/search?searchString=EBI- 81215&filter=ac&searchClass=Protein&view=partner&filter=achttp://www.ebi.ac.uk/intact/search/do/search?searchString=EBI- 81215&filter=ac&searchClass=Protein&view=partner&filter=ac

4. What is its function and where is it found? Gene Ontology Gene Ontologies Normalized expression distribution for tissue type Top ten OntologyAnnotationEvidenceSource Molecular Function Histone acetyltransferase activityIEAGOA/IPI Signal transducer activityTASGOA/IPI Transcription coactivator activityIEAGOA/IPI Transcription coactivator activityIPIGOA/IPI Protein bindingIPIGOA/IPI Transcription factor activityTASGOA/IPI Transferase activityIEAGOA/IPI Zinc ion bindingIEAGOA/IPI Biological Process Regulation of transcription, DNA-dependentIEAGOA/IPI Regulation of transcription, DNA-dependentTASGOA/IPI Response to hypoxiaTASGOA/IPI HomeostasisNASGOA/IPI Signal transductionNASGOA/IPI Protein complex assemblyTASGOA/IPI Cellular Component CytoplasmTASGOA/IPI NucleusIEAGOA/IPI NucleusTASGOA/IPI Tissue Normalized Expression (%) Cluster Clones : Tissue clones posterior tongue (pooled):22.022:473 Brain:10.611:491 liposarcoma:5.311:980 lymph:3.8415:20369 Trabecular meshwork:3.652:2854 metastatic prostate bone lesion:3.242:3214 fibrotheoma:2.513:6234 prostata:2.211:2355 salivary gland:2.071:2521 myeloid cells, 18 pooled CML cases, BCR/ABL rearrangement positive, includes both chronic phase and myeloid blast crisis: 2.011:2589

5. What makes up the coding sequence? It is made of 32 exons and 31 introns. The mRNA itself is 8.7 kb, 7.3 of that is coding!

6. Enough about its genome, lets talk protein! The protein is made of 2442 amino acids and is 265 kDa! That’s nice, but what does it look like?

7. Seven Different Domains Bromodomain Zinc finger ZZ typeTAZ zinc finger KIXTwo Domains of unknown functions (interact with other pfams Creb binding

8. So now that I know what its made of and where its found…. What does it do? Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. CREBBP, as coactivator, augments the activity of phosphorylated CREB to activate transcription of cAMP- responsive genes. What do we know about cAMP and memory? pg.223

9. Sounds nice, but what does that have to do with memory? http://www.dnai.org/text/mediashowcase/index2.html?id=483 CREB turns on other genes to store in long term memory. Switched on to create new connections between nerve cells Turning off and on genes by the act of remembering. In other words, CREB is a gene that mediates long-term memory. It acts as a master gene that turns on other genes, assisted by CREBBP Evidence for this function- studies on CREBBP transgenic mice suggests that competition for CBP plays an important role in regulating gene expression during cell growth. CREBBP and p300 function as transcriptional coactivators in the regulation of gene expression through various signal transduction pathways

10. Diseases associated with CREBBP Rubinstein-Taybi syndrome Result of germline mutation of CREBBP myeloid leukemias MLL translocations involving the CREBBP gene have primarily been reported in treatment-related acute myeloid lukemia after chemotherapy for other primary malignancies using topoisomerase II inhibitors.

11. References Ridley, Matt. "Chromosome 16, Memory." Genome, The Autobiography of a species in 23 Chapters. New York: Harper Perennial, 1999. 219-230. http://www.dsi.univ-paris5.fr/genatlas/fiche.php?symbol=CREBBPhttp://www.dsi.univ-paris5.fr/genatlas/fiche.php?symbol=CREBBP (slide 2,6) http://atlasgeneticsoncology.org/Genes/CBPID42.htmlhttp://atlasgeneticsoncology.org/Genes/CBPID42.html (slide 10) http://genome-www5.stanford.edu/cgi- bin/source/sourceResult?criteria=CREBBP&choice=Gene&option=Symbol&organism=Hs http://genome-www5.stanford.edu/cgi- bin/source/sourceResult?criteria=CREBBP&choice=Gene&option=Symbol&organism=Hs (slide 4, 8) http://www.ihop-net.org/UniPub/iHOP/gismo/87420.htmlhttp://www.ihop-net.org/UniPub/iHOP/gismo/87420.html (slide and 9) http://www.ncbi.nlm.nih.gov/genome/guide/human/http://www.ncbi.nlm.nih.gov/genome/guide/human/ (slide 1) http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uid s=1387http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uid s=1387 (slide 5) http://www.ebi.ac.uk/intact/search/do/search?searchString=EBI- 81215&filter=ac&searchClass=Protein&view=partner&filter=achttp://www.ebi.ac.uk/intact/search/do/search?searchString=EBI- 81215&filter=ac&searchClass=Protein&view=partner&filter=ac (slide 3) http://www.sanger.ac.uk/cgi-bin/Pfam/qquerypfam.pl?terms=crebbphttp://www.sanger.ac.uk/cgi-bin/Pfam/qquerypfam.pl?terms=crebbp (slide 7)